Copper transport is required for metabolism and persistence of Toxoplasma gondii
Pagura, L.; Todd-Nelson, J.; Merlet, C.; Hanna, J. C.; Faulds, L.; Chandrasekaran, S.; Park, S. C.; Koehler, K.; Sanchez-Rosario, Y.; Johnson, M. D.; Bissardon, C.; Cloetens, P.; Bowler, M. W.; Fairweather, S. J.; van Dooren, G. G.; Koshy, A. A.; Harding, C. R.
Show abstract
Copper is a conserved cofactor, required for essential processes including aerobic respiration. Pathogens subvert host copper; however the mechanisms of copper uptake are not well understood. Here, we identify and validate two copper transporters of Toxoplasma gondii and determine the role of copper in parasite metabolism and pathogenesis. We show that Ctr1 is required for copper uptake. Deletion leads to undetectable parasite-associated copper, a significant growth defect and a metabolic shift from mitochondrial respiration with to glycolysis. Absence of Crt1 was fully and rapidly rescued by exogenous copper, which we believe is transported through the lower-affinity transporter Ctr2. Ctr2 is dispensable in rapid growth, however, has a role in parasite persistence in chronic infection, both in vitro and in vivo. Together, these findings reveal for the first time a critical role for copper uptake in shaping metabolic plasticity, and highlights the importance of nutrient availability in regulating apicomplexan metabolism.
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